The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

France, Scott P.; Lewis, Russell D.; Martínez, Carlos A.

doi:10.1021/jacsau.2c00712

Cited by 51 publications

(39 citation statements)

References 116 publications

(182 reference statements)

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“…142 KREDs and ADHs have been widely used and engineered to synthesize chiral alcohols. 143 One example of site-selective KRED biocatalysis involves reduction of triketone 127 to the corresponding dihydro iso-alpha acid 128 (Scheme 22A). Directed evolution was used to engineer a site-selective KRED for this transformation.…”

Section: Carbonyl Reductionmentioning

confidence: 99%

“…Representative AKRs include aldose reductases, aldehyde reductases, hydroxysteroid dehydrogenases, ketoreductases (KREDs), and alcohol dehydrogenases (ADHs) . KREDs and ADHs have been widely used and engineered to synthesize chiral alcohols . One example of site-selective KRED biocatalysis involves reduction of triketone 127 to the corresponding dihydro iso-alpha acid 128 (Scheme A).…”

Section: Functional Group Manipulationmentioning

confidence: 99%

See 1 more Smart Citation

Non-Native Site-Selective Enzyme Catalysis

Mondal,

Snodgrass,

Gomez

et al. 2023

Chem. Rev.

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The ability to site-selectively modify equivalent functional groups in a molecule has the potential to streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary and secondary metabolism, but leveraging this capability for non-native substrates and reactions requires a detailed understanding of the potential and limitations of enzyme catalysis and how these bounds can be extended by protein engineering. In this review, we discuss representative examples of site-selective enzyme catalysis involving functional group manipulation and C–H bond functionalization. We include illustrative examples of native catalysis, but our focus is on cases involving non-native substrates and reactions often using engineered enzymes. We then discuss the use of these enzymes for chemoenzymatic transformations and target-oriented synthesis and conclude with a survey of tools and techniques that could expand the scope of non-native site-selective enzyme catalysis.

show abstract

Section: Carbonyl Reductionmentioning

confidence: 99%

Section: Functional Group Manipulationmentioning

confidence: 99%

Non-Native Site-Selective Enzyme Catalysis

Mondal,

Snodgrass,

Gomez

et al. 2023

Chem. Rev.

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show abstract

“…For example, organic substrates may have limited solubility in water, but this can often be solved by using a cosolvent or by modulating the substrate to be more soluble in water. In some instances, even poorly water-soluble substrates can still deliver high yields on process scales . In addition, if the enzyme is inefficient at catalyzing a desired reaction, the substrate can sometimes be engineered to more closely match the native substrate of the enzyme .…”

Section: Biocatalysis Todaymentioning

confidence: 99%

Enabling Broader Adoption of Biocatalysis in Organic Chemistry

Romero,

Saucedo,

Hernández-Meléndez

et al. 2023

JACS Au

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Biocatalysis is becoming an increasingly impactful method in contemporary synthetic chemistry for target molecule synthesis. The selectivity imparted by enzymes has been leveraged to complete previously intractable chemical transformations and improve synthetic routes toward complex molecules. However, the implementation of biocatalysis in mainstream organic chemistry has been gradual to this point. This is partly due to a set of historical and technological barriers that have prevented chemists from using biocatalysis as a synthetic tool with utility that parallels alternative modes of catalysis. In this Perspective, we discuss these barriers and how they have hindered the adoption of enzyme catalysts into synthetic strategies. We also summarize tools and resources that already enable organic chemists to use biocatalysts. Furthermore, we discuss ways to further lower the barriers for the adoption of biocatalysis by the broader synthetic organic chemistry community through the dissemination of resources, demystifying biocatalytic reactions, and increasing collaboration across the field.

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“…142 KREDs and ADHs have been widely used and engineered to synthesize chiral alcohols. 143 One example of site-selective KRED biocatalysis involves reduction of tri-ketone 127 to the corresponding dihydro iso-alpha acid 128 (Scheme 22A). Directed evolution was used to engineer a site-selective KRED for this transformation.…”

Section: Carbonyl Reductionmentioning

confidence: 99%

Non-Native Site-Selective Enzyme Catalysis

Mondal

Snodgrass

Gomez

et al. 2023

Preprint

View full text Add to dashboard Cite

The ability to a site-selectively modify equivalent functional groups in a molecule has the potential to streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary and secondary metabolism, but leveraging this capability for non-native substrates and reactions requires a detailed understanding of the potential and limitations of enzyme catalysis and how these bounds can be extended by protein engineering. In this review, we discuss representative examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization. We include illustrative examples of native catalysis, but our focus is on cases involving non-native substrates and reactions often using engineered enzymes. We then discuss the use of these enzymes for chemoenzymatic transformations and target-oriented synthesis and conclude with a survey of tools and techniques that could expand the scope of non-native site-selective enzyme catalysis.

show abstract

The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

Cited by 51 publications

References 116 publications

Non-Native Site-Selective Enzyme Catalysis

Non-Native Site-Selective Enzyme Catalysis

Enabling Broader Adoption of Biocatalysis in Organic Chemistry

Non-Native Site-Selective Enzyme Catalysis

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